CTNI-35. SURVIVAL BENEFIT OF ADDING OSIMERTINIB TO STANDARD SALVAGE TREATMENT REGIMENS FOR RECURRENT GLIOBLASTOMA (GBM) WITH EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) ALTERATIONS

Abstract Epidermal growth factor receptor (EGFR) is frequently mutated and/or amplified in GBM, playing a key role in its pathogenesis. Although EGFR-targeted therapies have shown limited success, the third-generation EGFR inhibitor, osimertinib (Osi), may offer clinical benefit. A retrospective case-control study was conducted to evaluate overall survival (OS) and adverse events (AEs) in recurrent GBM (rGBM) patients treated with Osi alongside other salvage therapies. Medical records of rGBM patients with EGFR alterations from 5/2018 to 5/2025 at UTHealth and Memorial Hermann at Texas Medical Center were reviewed. Clinical characteristics, salvage regimens, Osi treatment durations, AEs, imaging, molecular profiles, and laboratory results were reviewed and analyzed using Kaplan-Meier and hazard ratio methods. Non-Osi cohort is used as a control group. Among 78 rGBM patients (all IDH-wildtype) with EGFR alterations, 43 received Osi and 35 did not (non-Osi). Median age at diagnosis was 57 (Osi) vs, 59 (non-Osi), with methylated MGMT promoter in 37.2% vs, 54.3%, respectively. Over 97% completed standard adjuvant Stupp regimen. Salvage treatments are mixed including tumor treating fields (TTF), bevacizumab, irinotecan, laser interstitial thermal therapy, Gamma Knife radiosurgery, CCNU, checkpoint inhibitors, and investigational agents. Median OS was significantly longer in the Osi group: 26.2 months vs, 17.4 months (p = 0.00593). In the Osi group, 53.5% survived >24 months and 20.9% survived >48 months, compared to 17.1% and 0% in the non-Osi group. Survival benefits were consistent across age groups, MGMT status, prior surgery type and extend of resection. The longest OS (33 months) was seen in the subgroup treated with Stupp regimen followed by Osi, bevacizumab, temozolomide, irinotecan, and TTF. No unexpected AEs occurred. Reversible grade 3–4 AEs (16.3%) include thrombocytopenia (4), hypertension (1), decreased cardiac ejection fraction (1), and skin lesion (1). Grade 1–2 AEs (55.8%) are gastrointestinal symptoms, rash, and fatigue. These findings suggest Osi with salvage therapies may improve survival in EGFR-altered rGBM with manageable toxicity. Prospective trials are warranted.